Rejection after organ transplantation occurs when the immune system, which intrinsically defends the living body against bacteria, viruses, and so on, recognizes the graft as a “foreign substance”. It is not an exaggeration to say that the success of medical transplantation hinges on how to take effective control of such rejection. The rejection control method reportedly includes a method involving locally controlling graft rejection and a method involving controlling systemic rejection response itself. The latter method is mainly practiced at present. The administration of calcineurin inhibitors (e.g., cyclosporin and tacrolimus) or steroidal drugs is widely carried out in order to suppress rejection after transplantation, but is also known to often cause adverse reactions.
In recent years, methods for artificially inducing immune tolerance have been developed for the purpose of reducing the doses of drugs. Such methods involve extracting T cells from donors or recipients, mixed-culturing the T cells with specific antibodies, and returning the resulting cells to their bodies. There have been proposed, for example: an agent for suppressing kidney transplantation rejection, containing recipient-derived T cells as an active ingredient, the T cells being obtained by collecting T cells from the recipient scheduled to receive kidney transplantation and stimulating the collected T cells with alloantigen from a kidney donor in the presence of an anti-CD80 antibody or its antigen-binding fragment and an anti-CD86 antibody or its antigen-binding fragment (see e.g., Patent Document 1); a method for reducing the influence of graft versus host disease, comprising the steps of: extracting, from a human donor, a sample comprising peripheral blood mononuclear cells comprising CD4+CD25+ regulatory T cells; concentrating the CD4+CD25+ regulatory T cells in the sample to thereby form concentrated CD4+CD25+ regulatory T cells; proliferating the population of the concentrated CD4+CD25+ regulatory T cells; and administering a portion of the proliferated CD4+CD25+ regulatory T cells to a human to treat the graft versus host disease (see e.g., Patent Document 2); and a method for inducing recipient cells so that rejection after transplantation is reduced, the method comprising a) isolating peripheral mononuclear blood cells from a recipient and a donor, b) mixing ex vivo the cells of the donor and the recipient, c) treating the resulting cells with a regulatory composition, d) increasing the number of the cells, and e) introducing the cells into the recipient (see e.g., Patent Document 3).
Other known techniques include: an organ preservation solution comprising flavonoid glycoside (see e.g., Patent Document 4); an agent for preserving an organ, containing 1,5-anhydrofructose or its derivative (see e.g., Patent Document 5); an agent for preserving an organ, containing fullerenes (see e.g., Patent Document 6); an organ preservation solution containing a hepatocyte growth factor (HGF) (see e.g., Patent Document 7); an organ preservation solution containing lecithinized superoxide dismutase (see e.g., Patent Document 8); and an agent for preserving an organ, comprising glucosyl-L-ascorbic acid or a salt thereof (see e.g., Patent Document 9).
Meanwhile, ALA is known as an intermediate in tetrapyrrole biosynthesis pathways present in a wide range of animals, plants, or bacteria. This acid is commonly biosynthesized from succinyl CoA and glycine by 5-aminolevulinic acid synthase. Photodynamic therapy using ALA (hereinafter, also referred to as “ALA-PDT”) has also been developed and has received attention as a low invasive treatment method capable of maintaining QOL. For example, diagnostic or therapeutic agents for tumor comprising ALA and so on have been reported. In addition, ALA is also known to be useful as a preventing and improving agent or a therapeutic agent for adult disease, cancer, or male sterility (see e.g., Patent Documents 10 to 12).